A blood gas analysis is performed on many hospital patients both during and after surgery. The three parameters of interest are the partial pressures of oxygen (PO.sub.2) and carbon dioxide (PCO.sub.2), and the negative logarithm of hydrogen ion activity, the pH. These three parameters give a good indication of a patient's cardiac, respiratory and circulatory functioning, and the rate of metabolism. Monitoring the level of oxygen gas in the blood is important for determining the amount of oxygen being delivered to the tissues.
Several sophisticated blood gas analyzers are commercially available for analyzing blood samples after the blood is extracted from the patient (in vitro). However, the withdrawal and subsequent analysis of a blood sample is both cumbersome and time-consuming and does not permit continuous monitoring of the dissolved gases in a patient's blood. There has been a need for many years for a system which would enable blood gas measurements to be made directly in the patient (in vivo), thereby avoiding the difficulties and expense inherent in the in vitro techniques.
Among the suggestions in the prior art was the use of indwelling electrode probes for continuous monitoring of the blood gas. The in vivo electrode probes have not been generally acceptable. Two principal disadvantages of electrode probes are the danger of using electrical currents in the body and the difficulty of properly calibrating the electrodes.
Also among the suggested techniques for in vivo measurement has been the use of fiber optic systems. In a fiber optic system, light from a suitable source travels along an optically conducting fiber to its distal end where it undergoes some change caused by interaction with a component of the medium in which the probe is inserted or interaction with a material contained in the probe tip which is sensitive to (i.e., modified by) a component in the medium. The modified light returns along the same or another fiber to a light-measuring instrument which interprets the return light signal.
Fiber optic sensors appear to offer several potential benefits. A fiber optic sensor is safe, involving no electrical currents in the body. Optical fibers are very small and flexible, allowing placement in the very small blood vessels of the heart. The materials used, i.e., plastic, metal, and glass, are suitable for long-term implantation. With fiber optic sensing, existing optical measurement techniques could be adapted to provide a highly localized measurement. Light intensity measurements could be processed for direct readout by standard analogue and digital circuitry or a microprocessor. However, although the potential benefits of an indwelling fiber optic sensor have long been recognized, they have not yet been realized in widely accepted commercial products. Among the principal difficulties has been in the development of a sensor in a sufficiently small size which is capable of relatively simple and economical manufacture so that it may be disposable.
An oxygen sensor based on oxygen-quenched fluorescence is described in U.S. Pat. No. Re. 31,879 to Lubbers et al. Lubbers et al. describe an optode consisting of a light-transmissive upper layer coupled to a light source, an oxygen-permeable lower diffusion membrane in contact with an oxygen-containing fluid, and a middle layer of an oxygen-quenchable fluorescent indicating substance such as pyrenebutyric acid. When illuminated by a source light beam of a predetermined wavelength, the indicating substance emits a fluorescent beam of a wavelength different from the source beam and whose intensity is inversely proportional to the concentration of oxygen present. The resultant beam emanating from the optode, which includes both a portion of the source beam reflected from the optode and the fluorescent beam emitted by the indicating substance, is discriminated by means of a filter so that only the fluorescent beam is sent to the detector. In a second embodiment, the optode consists of a supporting foil made of a gas-diffusable material such as silicone in which the fluorescent indicating substance is randomly mixed, preferably in a polymerization type reaction, so that the indicating substance will not be washed away by the flow of blood over the optode. Lubbers et al. assert that both optodes can be adapted for in vivo use by disposing the same at the distal end of a catheter containing a pair of optical fibers for the incident and outgoing beams. However, the multi-layer optode of the first embodiment would be difficult to miniaturize. Lubbers et al. fails to disclose any method for attaching the alternative supporting foil to the distal end of the optical fibers or catheter. Furthermore, these sensors require at least two optical fibers which further limits miniaturization of the device.
Another PO.sub.2 sensor probe utilizing an oxygen-sensitive fluorescent intermediate reagent is described in U.S. Pat. No. 4,476,870 to Peterson et al. The Peterson et al. probe includes two optical fibers ending in a jacket of porous polymer tubing. The tubing is packed with a fluorescent light-excitable dye adsorbed on a particulate polymeric support. The polymeric adsorbent is said to avoid the problem of humidity sensitivity found with inorganic adsorbents such as silica gel. The probe is calibrated by using a blue light illuminating signal and measuring both the intensity of the emitted fluorescent green signal and the intensity of the scattered blue illuminating signal. Again, it is difficult to miniaturize the Peterson et al. sensor tip wherein a porous particulate polymer is packed within an outer tubing.
U.S. Pat. No. 3,612,866 to Stevens describes another method of calibrating an oxygen-quenchable luminescent sensor. The Stevens device, designed for use outside the body, includes an oxygen-sensitive luminescent sensor made of pyrene and, disposed adjacent thereto, an oxygen-insensitive reference sensor also made of pyrene but which is covered with an oxygen-impermeable layer. The oxygen concentration is evaluated by comparing the outputs of the measuring and reference sensors.
A principal disadvantage of the prior art sensors is their large size which prohibits their use in the narrow blood vessels, such as the narrow vessels of the heart or those of neonates.
Another disadvantage with the prior art oxygen sensors is that the detected luminescence signal includes a great deal of background noise in addition to the oxygen-quenched luminescence. The noise consists of reflections of the incident signal and broadband luminescence generated by other components in the system, such as the optical fiber. It would be desirable to eliminate the background noise in order to obtain a more precise measurement of oxygen concentration.
An optical system for excitation of a temperature dependent phosphor with radiation and for detecting independent emissions therefrom in first and second wavelength ranges that give an indication of the temperature of the phosphor is disclosed in U.S. Pat. No. 4,459,044 to Alves. The disclosed system includes a light source which transmits light along an optical fiber and a pair of detectors for detecting the emission from the phosphor. However, the system operates in a continuous mode. As a result, the detectors receive the excitation signal as well as the emission from the phosphor and low noise operation is not achieved.
U.S. Pat. No. 3,971,941, issued July 27, 1976 to Sewell et al discloses a radiation detecting system for viewing and imaging wherein infrared radiation is converted to shorter wavelength radiation while preserving the spatial information of the target input. The disclosed system utilizes a gateable detector for temporal discrimination to eliminate the influence of short-term emissions from the quantum mechanical substance.
It is a general object of the present invention to provide an excitation and detection apparatus for use with a sensor comprising a phosphorescent material.
It is a further object of the present invention to provide excitation and detection apparatus for coupling signals to and from a sensor through an optical fiber.
It is yet another object of the present invention to provide excitation and detection apparatus for use with a sensor which emits long-lived luminescence including a measuring wavelength and a reference wavelength.
It is yet another object of the present invention to provide excitation and detection apparatus for use with an oxygen sensor comprising an oxygen-quenchable lanthanide complex.
It is still another object of the present invention to provide excitation and detection apparatus for use with a remotely located phosphorescent material wherein the detector is inhibited during a pulsed excitation signal to achieve low noise operation.